Amsterdam Cardiovascular Sciences

A novel research strategy to tackle cardiovascular problems caused by metabolic disorders

Diabetes is a major threat to health care in the Netherlands, with 1 million patients and an expected ~30 percent increase in prevalence in the next 15 years. As obesity figures are expected to double in this period, type 2 diabetes mellitus, the Metabolic Syndrome (MetSyn) and their co-morbidities will profoundly affect our health and economy.

Although it is clear that excess energy intake is the driving force for obesity, little is known about the processes that trigger the transition from the metabolically healthy to the metabolically unhealthy obese phenotype. In addition to the MetSyn, and closely linked to it, is the expanding prevalence of chronic kidney disease, which, like MetSyn has proven to be a key metabolic derangement involved in cardiovascular disease.

Both conditions share epidemiological features (like premature ageing, and increasing prevalence), pathophysiological mechanisms (like disturbed microcirculatory regulation) and clinically important cardiovascular complications.

Focus

• Pathogenesis of type 2 diabetes mellitus and diabetes-related syndromes
• New type 2 diabetes mellitus therapies
• Complications of diabetes
• Organ failure induced cardiovascular disease

Unique research expertise

• (Prospective) biobank studies and computational modeling
• Fecal microbiota transplantation studies
• Clinical and experimental models (e.g. mice) for microvascular dysfunction
• Renal failure and microvascular disease development

Infographics on research performed within the Diabetes & Metabolism research program:

Aim

Within ACS, the Amsterdam Diabetes Research Center (ADRC) aims to develop a novel integrated research strategy to tackle the cardiovascular problems caused by metabolic disorders in a concerted and effective way.

The ADRC will provide a framework connecting the renowned VUmc diabetes center to related metabolic research programs within Amsterdam UMC location AMC (metabolism and gastroenterology) and Amsterdam UMC location VUmc (the former ICaR-VU and EMGO).

An integrated, multidisciplinary research program will connect the different research groups, based on ongoing large-scale Amsterdam biobank research programs (e.g. HELIUS and Slotervaart-OLVG Bariatric surgery cohort), translational clinical research and modeling studies of diabetes, the MetSyn and their complications.

The aim of the ADRC is to become a Top Diabetes Research group within Europe within the next 5 years. The ADRC aims to translate new insights into rational and effective strategies to reduce the societal costs of diabetes and the metabolic syndrome.

Our overall goal is to lead in translational population-based, clinical and basic research focusing on insulin resistance, diabetes and metabolic derangements which lead to cardiovascular complications.

Program Leaders

Young ACS

Elena Rampanelli & Anna Emanuel

Research themes

Pathogenesis of type 2 diabetes mellitus and diabetes-related syndromes

Chronic low-grade inflammation (resulting from e.g. altered intestinal microbiome composition and nutrient overload) leads to microvascular dysfunction and peripheral insulin resistance in obese subjects.

This is followed by complex inter-organ communication involving the brain, endothelium, beta cell (inflammation), bone and bone marrow/immune cells, adipose tissue and symbionts (intestinal microbiome).

To disentangle this complex process, we will analyse datasets from different biobank studies (HELIUS, Hoorn and Slotervaart-OLVG Bariatric surgery cohort), and use combinations of computational models, developed in collaboration with the systems biology groups in UvA and VU/VUmc, and tissue-specific animal models.

New type 2 diabetes mellitus therapies

It is of utmost importance to dissect the underlying mechanisms that induce the comorbidities of the MetSyn and directly test and implement the diagnostic and therapeutic value of these discoveries in clinical diabetes care.

Clearly this requires a thorough understanding of the mechanisms inducing the metabolic imbalance in subjects characterized by malign obesity with insulin resistance as well as Type 2 diabetes. In this regard the pathophysiological mechanisms behind obesity- and diabetes-associated microvascular dysfunction, which predispose to e.g. nephropathy and heart failure, are incompletely understood.

The role of obesity and diabetes in diastolic heart failure is investigated in close collaboration with the Research Program Heart Failure & Arrhythmias. Early identification of persons at risk and understanding of preclinical pathology will be central to initiate proper treatment strategies and delay or reverse disease progression.

Organ failure-induced cardiovascular disease

Metabolic derangements due to organ failure represent a high risk for cardiovascular disease. However, systemic consequences of metabolic derangements are poorly understood. Impaired kidney function is a strong risk factor for mortality in heart failure patients.

Our current studies focus on the mediating effects of both early and advanced renal failure on cardiovascular function. The connection between kidney dysfunction and development of vascular and cardiac dysfunction is studied within (inter)nationally-funded research consortia.

PI's and ongoing research lines

The following PI's are member of the Diabetes & Metabolism Research Program:

PI’s and staff members of the Diabetes & Metabolism Research program were invited to give a short pitch about their research, funding and future plans for the coming years. This resulted in the figure presented below and an overview of missions along with slides for individual research lines (see Downloads). If your research is missing, please send an email to acs@amsterdamumc.nl with the ongoing research template (see Downloads).

Overview of collaboration within the D&M Research Program and with other ACS Research Programs. Lines represent ongoing collaboration between D&M PI's. Asterisks indicate program leaders: Marc Vervloet, Max Nieuwdorp and Ed Eringa.

Downloads

ACS research lines by D&M Principal Investigators:

Program members